Immune cell remodelling and the peribiliary immune niche in primary biliary cholangitis: from initiation to...

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease characterised by immune-mediated destruction of small intrahepatic bile ducts. Although ursodeoxycholic acid remains the standard first-line therapy and peroxisome proliferator-activated receptor agonists have expanded treatment options, current therapies do not fully address the immune mechanisms that drive disease initiation and persistence. Recent work suggests that PBC cannot be explained by abnormalities in a single immune-cell population but instead reflects coordinated immune remodelling around injured bile ducts. In this review, we organise current evidence within an overlapping, process-oriented framework encompassing immune initiation, effector amplification and immune-regulatory dysfunction. Stressed biliary epithelial cells provide autoantigens, immune-sensing signals and inflammatory cues while myeloid cells and lymphocyte subsets cooperate to sustain tissue-resident cytotoxic, inflammatory and profibrogenic circuits. Disease chronicity is further promoted by defective regulatory mechanisms, including impaired Treg stability and dysfunction of non-conventional regulatory populations. We also discuss mechanism-guided therapeutic strategies targeting effector T cells, myeloid inflammation, B-cell activation, immune tolerance and the cholestatic microenvironment. Understanding the peribiliary immune niche may facilitate immune phenotype-guided stratification and precision therapy in PBC.